甘草次酸衍生物受体靶向复方脂质体的制备及其体外释放研究  

Preparation and in Vitro Release of Glycyrrhetinic Acid-tanshinone ⅡA-salvianolic acid B Compound Liposomes with Glycyrrhetinic Acid Derivative as Targeting Molecule

作　　者：管辉达 王秀丽[1] 林珈好[1] 徐昕[1] 褚福浩[1] 王玉蓉[1] 

机构地区：[1]北京中医药大学中药学院,北京100102

出　　处：《世界科学技术-中医药现代化》2014年第10期2190-2196,共7页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：国家自然科学基金委青年项目(81202928):丹参-甘草不同极性组分受体介导肝主动靶向脂质体构建评价及共性问题探讨;负责人:王秀丽;北京市自然科学基金委面上项目(7123118):基于甘参药对治疗肝纤维的受体介导主动肝靶向脂质体的构建;负责人:王秀丽

摘　　要：目的:合成两亲性导向分子甘草次酸衍生物3-琥珀酸-30-硬脂醇甘草次酸酯(18-GA-Suc),研究其掺入甘草次酸—丹参酮ⅡA—丹酚酸B复方脂质体(GTS-Lip)的制备工艺,并考察其体外释放规律。方法:采用1HNMR和13CNMR表征18-GA-Suc的结构,通过单因素考察确定18-GA-Suc的投料量,低速离心法测定其掺入比率,比较修饰前后复方脂质体的理化性质,以平衡透析法考察甘草次酸衍生物受体靶向的甘草次酸—丹参酮ⅡA—丹酚酸B复方脂质体(Suc-GTS-Lip)中3种成分的体外释放规律。结果:优化的处方工艺为:18-GA-Suc投料量为膜材的10%(mol·mol-1),掺入比率为96.58%。Suc-GTS-Lip形态圆整,分布均匀,其中甘草次酸(GA)、丹参酮ⅡA(TSN)和丹酚酸B(Sal B)的平均包封率分别为86.15%,81.70%,91.05%,平均粒径为128.7 nm,平均Zeta电位为-15.5m V。GA和TSN体外释放规律符合Higuchi方程,Sal B体外释放规律符合Hixon-crowell方程。结论:甘草次酸衍生物(18-GA-Suc)能在脂质体膜上成功表达,本脂质体制备工艺稳定,GA、TSN和Sal B 3种成分在体外均具有一定的缓释作用,为进一步研究其肝靶向性奠定了基础。This article was aimed to study the preparation process of glycyrrhetinic acid（GA）-tanshinone IIA（TSN）-salvianolic acid B（Sal B） compound liposomes with 3-succinic-30-stearyl glycyrrhetinic acid（18-GA-Suc） which is one of amphiphilicglycyrrhetinic acid derivatives as targeting molecule. The structure of the targeting molecule was validated by ^1H-NMR and ^13C-NMR methods. The feed ratio of 18-GA-Suc was optimized through single factor test and the incorporation ratio of 18-GA-Suc was determined by low-speed centrifugation. Meanwhile, physicochemical properties between Suc-GTS-Lip and GTS-Lip were compared. In vitro release studies of three components in Suc-GTS-Lip were conducted by equilibrium dialysis method. The results showed that the optimum conditions were when the feed ratio of 18-GA-Suc was 10% lipid liposomal membrane（mol·mol^-1）. It revealed that the incorporation ratio of 18-GA-Suc was 96.58%, and the encapsulation efficiencies of GA, TSN, and Sal B were about 86.15%, 81.70%, and 91.05%, respectively. In addition, the Suc-GTS-Lip was spherical and uniformly dispersed with particle size of 128.7 nm and zeta potential of-15.5 m V. The release model of GA and TSN was fitted well with Higuchi equation, while Sal B was fitted well with Hixon-crowell equation. It was concluded that Glycyrrhetinic acid derivatives（18-GA-Suc） can be successfully expressed in the liposome membrane, and the optimal preparation method of Suc-GTS-Lip was stable. All three components encapsulated into liposomes had sustained-release effects, which laid a good foundation for its further study about liver-targeting.

关 键 词：甘草次酸衍生物 甘草次酸 丹参酮ⅡA 丹酚酸B 复方脂质体 处方优化 体外释放 

分 类 号：R737.9[医药卫生—肿瘤]